Microfluidic systems typically involve control of fluid flow through one or more microchannels. One class of systems includes microfluidic “chips” that include very small fluid channels and small reaction/analysis chambers. These systems can be used for analyzing very small amounts of samples and reagents and can control liquid and gas samples on a small scale. Microfluidic chips have found use in both research and production, and are currently used for applications such as genetic analysis, chemical diagnostics, drug screening, and environmental monitoring.
Another area in which microfluidic chips are being implemented is in protein crystallization. Crystallization of proteins in microfluidic systems is advantageous over conventional crystallization techniques because microfluidic systems can allow high-throughput analysis of many samples simultaneously. Thus, sample conditions can be varied and tested in parallel using much smaller quantities of reagents, resulting in faster and less costly analysis.
Several publications have described the use of microfluidic chips for crystallization of proteins. For example, International Patent Publication No. WO 2004/038363 demonstrates reactions that can occur in plugs transported in the flow of a carrier-fluid, and U.S. Patent Publication No. U.S. 2003/0061687 shows high-throughput screening of crystallization of a target material by simultaneously introducing a solution of the target material into a plurality of chambers of a microfabricated fluidic device. Although these systems may allow crystallization of proteins in small volumes, nucleation and growth of crystals in each of these systems is irreversible, thus offering less control over processes of crystallization than in reversible systems. The present invention provides a device that allows reversibility of crystal nucleation and growth, as well as decoupling of nucleation and growth, while retaining the virtues associated with microfluidics including high-throughput, low-volume, precise metering, and automated processing of samples.